台湾大学附属医院抗生素使用培训精选文档

1、 全民健康保險醫院醫療費用審查注意事項對於以痰之培養結果做為使用高價抗生素者, 應注意是否適當, 嚴加審查應優先使用第一線抗生素使用抗生素, 原則上以同時不超過兩種為限, 否則需附相關之微生物學培養結果抗生素誤用的不良後果 非醫學使用，或醫療時過度使用: - 破壞微生物生態平衡，促成抗藥性細菌散佈，後患無窮。抗生素引起之不良反應。不必要之藥費支出，消耗醫療資源。應使用而未使用，或延誤使用: - 耽誤病情造成不必要之併發症甚至死亡，有醫療糾紛之危險。為治療併發症需額外之加護病房照護或外科手術，消耗醫療資源。診療方向不正確:合理的使用抗生素- 是否有足夠的證據使用抗生素- 使用抗生素之前是否有做好

2、病原體檢查- 那些微生物為可能之致病原- 對於已知致病菌，是否仍需使用後線抗生素- 需要合併使用抗生素治療嗎 - 宿主因素，抗生素穿透力- 給藥方式(注射或口服)，抗生素劑量，毒性， 抗生素使用時間- 前次使用抗生素之種類，是否為抗藥性病原#1.是否有足夠的證據使用抗生素?全民健康保險藥品給付規定摘錄(2004. 7. 12)10.抗微生物劑 10.1.抗微生物劑用藥給付規定通則 3. 上呼吸道感染病患如屬一般感冒 （common cold）或病毒性感染者，不應使用抗生素。如需使用，應有細菌性感染之臨床臨床佐證，例如診斷為細菌性中耳炎、細菌性鼻竇炎、細菌性咽喉炎，始得使用抗生素治療（90/2/

3、1增訂）。 急性上呼吸道感染抗微生物製劑建議治療準則 中華民國感染症醫學會（2002. 3. 2）lcommon cold with mucopurulent nasal discharge does not mean bacterial infectionlacute pharyngotonsillitis: (a) symptoms highly suggestive of streptococcal pharyngitis are: severe sore throat, exudative pharyngitis, and cervical lymphadenopathy (b) sy

4、mptoms not suggestive include cough, rhinorrhea, pharyngeal ulcer, diarrhea, and conjunctivitisnote: j microbiol immunol infect 2002; 35: 272急性上呼吸道感染抗微生物製劑建議治療準則 中華民國感染症醫學會（2002. 3. 2） diagnosis drug of choice alternativecommon cold acute pharyngotonsillitis : streptococcal penicillin v macrolides,

5、1o cephem, clindamycinacute sinusitis amoxicillin augmentin, 2o oral cephem acute otitis media amoxicillin augmentin, 2o or 3o oral cephemacute bronchitis influenza* amantadine (a only) oseltamivir j microbiol immunol infect 2002; 35: 272 #2.在使用抗生素之前是否已取得臨床檢體做好病原體培養：革蘭式染色及各種培養?advantages and disadva

6、ntages of gram smear in pneumoniaadvantagesquick and inexpensivequality of sputumaid interpretation of cultures resultsearly indication of possible etiologydisadvantagescriteria for interpretationexperience of lab operatorcorrelates poor with culture results及早使用抗生素敗血症或敗血性休克的病人。疑似細菌性腦膜炎、急性心內膜炎的病人。白血球

7、缺乏而有發燒的病人。有明顯部位感染情形。病人為老年人、幼童或有免疫機能缺損者院內感染。經驗性療法 (empirical therapy)可能是嚴重感染症的前驅症兆persisted hyperpyrexia 39ocshaking chillsappearance of skin lesionschange of mental statusdic with thrombocytopeniahemolysistachypnea, hyperventilation or respiratory alkalosishypotension, shock, increased fluid volume

8、requirementsevere localized painmetabolic acidosisoliguriamodified from young ls. fever and septicemia. in: rubin rh, young ls. clinical approach to infections in compromised host. 2nd ed. 1994thrombosisdiclivedo reticularisvascular phenomenon of sepsis#3.那些微生物為可能之致病原?staphylococcus aureusstreptococ

9、cus pneumoniaeklebsiella pneumoniaelegionella pneumophilia69 y/o male, smoking for 40 years.檢體名稱：sputum 報告: 1. serratia marcescencs (3+)2. viridans streptococcus (3+)3. neisseria species (3+) am: ampicillin ramc: amoxi./clavu r cz: cefazolin rcmz: cefmetazole rctx: cefotaxime rgm: gentamicin 10g ran

10、: amikacin sipm: imipenem scip: ciprofloxacin rfep: cefepime razm: aztreonam rtrue pathogen? colonization?1.這是真的嗎?先確定病原是否有意義血液或無菌體液培養(腦脊髓液，肋膜積水.).痰液培養：聽診有囉音或敲診有濁音新發生的膿痰或是痰液的顏色改變。血液培養陽性或由bronchial washing或biopsy培養出菌。肺部x光有新增或惡化的浸潤，開洞或肋膜積水。泌尿道培養：泌尿道症狀及尿液培養有大於105菌落/ml。培養出的微生物需小於三種。泌尿道症狀加上wbc esterase或ni

11、trate陽性，或膿尿(10 wbc/hpf)或重複培養出同一之細菌102菌落/ml。傷口培養：必須要有膿液或紅腫熱痛存在，不可只是單純的根據傷口培養結果用藥。 am j infect control 1988;16:128-40. positive sputum, urine, bile, stool, skin swab culture but without symptoms原則上不建議使用抗生素例外: asymptomatic bacteriuria before urological work up and in pregnancy should be treatedcoagulas

12、e-negative staphyloccistaphylococcus epidermidisviridans streptococcimicrococcibacillus speciescorynebacterium species neisseria speciesnonfermentative gram-negative bacilli lacaligenes, flavobacterium, sphingomonas. #4. 對於可能致病的微生物，若已知有多種抗生素有效，該選擇何種抗生素? 參考drug of choice guidelines costs肺炎抗微生物製劑建議治療準

13、則 中華民國感染症醫學會（1999. 3. 7） drug of choice alternativecommunity-acquired pneumonia adults (60 y) mild-moderate pcn or 2o cephem unasyn/aug/fq macrolides /tetracyclines severe 3o cephem ag timentin/tazocin/4ocephem macrolides /fq ag macrolides aspiration pneumonia pcn or clindamycin unasyn/aug/cefoxitin

14、/cef- metazole/pcn+anergynhospital-acquired pneumonia mild-moderate 2o or 3o cephem or timentin/tazocin/azactam/ unasyn/aug ag fq ag j microbiol immunol infect 1999; 32: 292-294. #5.需要合併使用抗生素治療嗎? antibiotics combination- synergistic effectskuo lc, et al. clin microbiol infect 2007; 13: 196-8.mdr-aci

15、netobacter baumannii bacteremia 加成作用(synergism)多重細菌感染(如腹腔內、骨盆腔感染)避免多重抗藥性菌株出現合併抗生素使用之優點合併抗生素使用之缺點藥物毒性機會增加高抗藥性菌株移生而造成另一波感染拮抗作用花費較高enterococci or pneumococcilpenicillin + gmlvancomycin + (? gm) or rifampinlpcn + fqmrsalvancomycin (or teicoplanain ) + gm or rifllinezolid + gm or riffor drug-resistant gp

16、clfor pseudomonas, drug-resistant e. coli, kp, proteuslprevent emergence of resistant mutantlanti-pseudomonal b-lactams + gm/amklfqs + b-lactams or fqs + carbapenemslfqs + aminoglycosides - still controversial ! for drug-resistant gnb#6.宿主因素who are you dealing with?old vs. youngcommunity vs. hospita

17、lizedsubstance abuse, prosthesis in placebarrier disruption and anatomic abnormalypre-existent medical or surgical illnessimmune-competent vs. -compromizedltypes of immune suppression (steroid) or therapies administeredseverity of the diseases.泌尿道感染抗微生物製劑建議治療準則 中華民國感染症醫學會（2000. 3. 11） drug of choice

18、 alternativeasymptomatic bacteriuria non-pregnant* pregnant 1o or 2o cephem amoxicillin (for enterococci)acute bacterial cystitis non-pregnant tmp/smz, dolcol fq, amoxicillin pregnant 1o or 2o cephem amoxicillin acute uncomplicated pyelonephritis (apn) 1o or 2o cephem ampicillin, ag acute prostatiti

19、s 3ocephem or fq tmp/smz j microbiol immunol infect 2000; 33: 271-272. #7. 藥物動力學哪種給藥方式(靜脈注射或口服)較為合適time-dependent antibioticsauc/mic 125 40 50%concentration-dependent antibioticscmax/mic 8-12 xonce-daily dose of aminoglycosidescharacteristics in pharmacology:concentration-dependent bacterial killing

20、post-antibiotic effect (pae): neutrophil dependentadaptive resistance of bacteria during prolong exposuretoxicity more related to long exposure time and less related to transient high serum leveldosage: (ibw) gentamicin, tobramycin, netilmicin: 3-5 mg/kg/day amikacin, streptomycin: 12-15 mg/kg/dayse

21、rum level monitor 72 hrs after use: check trough level only! adjust dosing interval! no loading dosenot to use once daily doseccr20% tbsa)pregnancy*, children*neutropenic feverendocarditis; enterococciliver cirrhosis with decompensation*avoid aminoglycosides#8.抗生素合適的劑量loading dose of vancomycinsubop

22、timal conc. of vancomycin with 7.5 mg/kg q6h during first 48 hoursloading dose with vancomycin 25 mg/kg (約 1 -1.5 g) increase drug concentration during 24 48 hrsfor difficult mrsa infections trough of vancomycin 15 ug/mlwang jt, et al. j antimicrob chemother 2001teicoplanin 成年人臨床使用劑量針對敗血性關節炎、重度燒燙傷或心

23、內膜炎者l起始劑量：12 mg/kg (約800毫克)l維持劑量：靜脈注射12 mg/kg，給藥間隔視腎功能而定起始劑量維持劑量 (第四天起)腎功能正常者連續三劑靜脈注射 6 mg/kg (約400 mg) q12h每天靜脈注射 6 mg/kg (約400毫克)腎功能中度損壞者隔天靜脈注射 6 mg/kg (約400mg)嚴重腎衰竭每三天靜脈注射 6 mg/kg (約400mg)38with / without loading dose6.4710.8011.228.666.114.24jac 2003;51:9715.empiric antibiotic for nosocomial pne

24、umonia with multidrug resistant bacteriaanti-pseudomonal b-lactamscefepime 1-2g q8-12h cefpirome 1-2g q8-12hceftazidime 2g q8h imipenem 500mg q6h - 1g q8hmeropenem 1g q8h q6hpiperacillin-tazobactam 4.5g q6h aztreonam 2 g q6-8h*doses are based on normal renal and hepatic function of adult(us-hap guid

25、elines 2005)aminoglycosidesgentamicin 5-7mg / kg / day*tobramycin 5-7mg / kg / day*amikacin20mg / kg / day*quinoloneslevofloxacin 750mg qdciprofloxacin400mg q8hindication of maximal dosebetter tissue penetrationlmeningitis and cns infection lendocarditislseptic arthritis and osteomyelitislempyemasep

26、tic shock or other life-threatening infectionsborderline susceptible pathogens依腎功能調整抗生素劑量tetracyclines, gentamicin, sulfonamides, polymyxins, vancomycin, penicillins (oxacillin除外), cephalosporins, acyclovir. 加重因子: 脫水,年紀大,同時合併腎毒性藥物,本身腎功能不好,低體重. 可給予充足水份減少腎毒性腎毒性: creatinine上升上升0.5mg/dl.不一定會水腫或乏尿.ideal

27、body weight vs. real body weight ibw = ( bh - 80) x 0.7 in male patients ibw = ( bh - 70) x 0.6 in female patients* estimated ccr = ( 140 - age ) x bw 72 x crecalculating the dosage using ibw and estimated ccr* 0.85 in female patients use ibw in obese patients#9.抗生素在培養結果出來後是否需要改藥或進一步調查?de-escalation

28、 therapy (降階治療) 減少不必要的抗生素以避免抗藥性發生 給予足夠的抗生素以改善患者預後2一旦培養出較不抗藥之致病菌則應考慮降階治療抗生素為何無效delay in initiation of appropriate therapywrong diagnosis: non-infectious inflammatory process, non-bacterial infectionmisinterpretation or errors derived from susceptibility results: in vitro discrepancy; inappropriate in

29、terpretationinadequate concentration drugs at site of infection: inadequate dose, drug interaction, poor delivery (vascular diseases, obstruction, permeability barrier)抗生素為何無效decreased activity at site of infection: lph (aminoglycoside)lbiofilm formation, decreased metabolic activity of microorganism (vegetation, foreign body)laccumulation of pus, presence of dead bone or necrotic tissuehost factors: immunodeficiencydevelopment of drug resistancesuperinfection or multiple infections#10. 抗生素使用的時間抗生素治療期間一般感染症(肺炎、腦炎、腹膜炎、膽管炎、骨盆腔炎、手術傷口血流,呼吸道,上泌尿道,腸胃道感染)